The objective of the present study is to assess the possibility of immunization with a vaccine against periodontal disease, which is the most common cause of tooth loss in adult humans over the age of 40. Treatments are expensive and therefore not available to everyone. In previous studies with Macaca fascicularis we found that immunization with a vaccine aimed at Porphyromonas gingivalis, a common bacterium associated with periodontal disease, prevented the progression of periondontal disease. Because similar findings have not been reported elsewhere, and the mechanisms involved in the prevention of the disease were unclear, we have undertaken this project to study the messengers of inflammation (cytokines such as IL-1b, TNA-a and PGE2) and to analyze antibody titers in saliva and serum in immunized and control animals. Analysis of clinical data and radiographs will not be performed until all animals have completed the study. However, our studies of gingival fluid from inflamed periodontal sites show that levels of TNF-a and PGE2 are significantly lower in the immunized animals, thus supporting the hypothesis that immunization is effective in controlling the inflammatory process that results in bone and tooth loss. In addition to our studies of cytokines in the gingival fluid, we have been working on methods for studying cytokines in gingival tissues. For this purpose we have obtained gingival biopsies from a subset of the animals enrolled and from animals in the tissue donor program. In the current year we plan to analyze the antibody levels in serum and saliva, determine the presence of cytokines in fluid from the inflamed sites, and begin analyzing clinical data.